The Skull Could Be Playing an Immune System Role for the Brain

Conventionally, the skull has largely been known as a structure which forms a protective casing around the brain. However, a recent study conducted by a team at WashU Medicine has found structures similar to lymph nodes inside the bone marrow in the skull, suggesting that the brain may have a local defense system that mobilizes an immune response in case a disease develops in the brain. 

The study, together with a few other recent discoveries, challenges the long-held view that the immune system and the brain operate separately. 

Prof. Jonathan Kipnis, an immunology and pathology specialist at WashU Medicine, was the study’s lead author. He explains that their work shows that the bone marrow within the skull plays a bigger role than was previously acknowledged. He adds that these structures contain hubs that control immune responses that are localized within the brain. 

For their study, the researchers tracked proteins and observed that they moved from the brains of mice into tiny channels that led into the bone marrow inside the skull. In this bone marrow, the team observed structures that are typically linked to lymph nodes. 

In the body, lymph nodes are the sites where immune responses are trained for. In those sites, antibodies are produced in follicular cells so that infections and diseases can be fought. Jang H. Park, the first author of the study, says they were excited to make this discovery because it was the first time such a function was observed in the bone marrow found within the skull. 

Park says that what they observed suggests that the brain appears to have its own immune structures that are focused on addressing its needs. 

The team then wanted to find out whether the lymph node-like hubs actually played any role in the face of a disease. To test their hypothesis, they leveraged a glioblastoma mouse model and then introduced a drug to disrupt the immune hubs inside the skull. Brain cancer tumors grew rapidly in those models when compared to other models that hadn’t had a disruptive drug introduced in the skull. 

This shows that the brain’s localized immune system was activated and mounted a defense against the cancer. Later, activity was observed in lymph nodes located in other parts of the body, showing that the brain had its own first responders but subsequently got help from the rest of the body. 

The researchers then boosted the immune response in the skull by introducing a targeted therapy. The anticancer response was even more pronounced, opening the door to developing treatments for brain cancer that can be introduced directly into the skull. This could spare nearby tissues and the rest of the body from being adversely affected by drugs used to fight brain cancer. 

A lot of work lies ahead to translate these preclinical research findings into clinical applications, but the door has been opened. It remains to be seen whether a time may come when brain cancers can be treated using therapies developed by entities like CNS Pharmaceuticals Inc. (NASDAQ: CNSP) by delivering those treatments directly into the skull. 

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